A successful drug development program requires a complete understanding of the clinical pharmacology of the agents being evaluated. The Clinical Pharmacology Section (CPS) has as its primary interest the use of pharmacokinetic and pharmacodynamic concepts in the development of novel anticancer agents. The CPS is directly responsible for the pharmacokinetic/pharmacodynamic analysis of numerous Phase I and II clinical trials conducted within the NCI. In addition, the CPS provides direct pharmacokinetic support for many studies performed elsewhere in the extramural community. Within the section, we utilize compartmental and noncompartmental approaches to define the disposition of agents. Also, we are often required to characterize the plasma protein binding properties and metabolism of new agents through in vitro techniques. Several of our clinical trials have used adaptive control with a feedback mechanism to target particular plasma concentrations (e.g., suramin, CAI). The drugs with which the CPS has had its greatest experience include: suramin, phenylacetate, phenylbutyrate, TNP-470, PMEA, AZT, PSC 833, CAI, DAB486IL2, IgG-RFB4-SMPT-dgA CD22, IgG-HD37-SMPT-dgA CD19, ormaplatin, UCN-01, flavopiridol, thalidomide, 9AC, intraperitoneal cisplatin, intraperitoneal carboplatin, depsipeptide, docetaxel, perifosine, and paclitaxel. Currently, we are characterizing the pharmacokinetics of multiple day dosing of PSC 833 when administered with vinblastine and paclitaxel. This is an attempt to characterize any interactions between PSC 833 and either of these agents both in the clinical pharmacokinetic data, as well as through in vitro metabolism studies. Recently, we have completed a Phase I trial of COL-3, a matrix metalloproteinase inhibitor. We are initiating a Phase I trial of CC5013 and 2ME, both angiogenesis inhibitors.